Welcome to my channel MK
MediGuide Lectures, learning with artworks like drawing and calligraphy. In
this lecture, we will discuss the interrelationship between the cytokine storm
and aging. Strangely, plenty of evidence has been shown that the severity of COVID-19
infections vary widely from children usually asymptomatic, adults with a mild infection,
as well as elderly adults appear
to be more severe typically deadly critical. It has proven that COVID-19 infection
in some elderly critical adults leads to a cytokine storm, which is characterized by severe
systemic elevation of several pro-inflammatory cytokines. Then, a
cytokine storm can induce edematous, ARDS, pneumonia, as well as multiple organ
failure in aged patients. It is far from clear till now that why cytokine storm
induced in only COVID-19 elderly patients, and not in young patients. Answer to
this question is it seems that cytokine storm phenomena is associated with age
because Aging is related to
increased levels of systemic pro-inflammatory cytokines and decreased levels of
anti-inflammatory cytokines. Ample studies have indicated elevated levels of
interleukin (IL)-6, IL-1, tumor necrosis factor-α (TNF α), as well as C-reactive protein (CRP) in aged subjects. among
other cytokines, these cytokines are reported to be high in patients with severe
cases of COVID-19. In which IL-6 plays a key role in contributing to cytokine
storm. Accordingly, it seems that increased generation of
pro-inflammatory markers due to SARS-CoV 2 and aging have a critical role in
the process of cytokine storm in severe COVID-19 patients. Although,
the exact underlying mechanism of cytokine storm in elderly adults with severe COVID-19
infection is far from clear. However, It seems that “cytokine storm” the phenomenon in elderly patients with severe COVID-19 infection is associated
with many age-related pathophysiologic processes, including alteration of
angiotensin-converting enzyme 2 (ACE2) receptor expression, excess ROS
production, alteration of autophagy, senescent adipocytes activity mean the
inflammatory phenotype of senescent cell activity, particularly adipose tissue,
and immune-senescence, as well as lack of vitamin D content. Here, we are going
to review and discuss all above mentioned age-related pathophysiological pathways
that appear to contribute to the dysregulation of cytokine networks and
possibly a cytokine storm in elderly patients with severe COVID-19 infection.
MediGuide Lectures, learning with artworks like drawing and calligraphy. In
this lecture, we will discuss the interrelationship between the cytokine storm
and aging. Strangely, plenty of evidence has been shown that the severity of COVID-19
infections vary widely from children usually asymptomatic, adults with a mild infection,
as well as elderly adults appear
to be more severe typically deadly critical. It has proven that COVID-19 infection
in some elderly critical adults leads to a cytokine storm, which is characterized by severe
systemic elevation of several pro-inflammatory cytokines. Then, a
cytokine storm can induce edematous, ARDS, pneumonia, as well as multiple organ
failure in aged patients. It is far from clear till now that why cytokine storm
induced in only COVID-19 elderly patients, and not in young patients. Answer to
this question is it seems that cytokine storm phenomena is associated with age
because Aging is related to
increased levels of systemic pro-inflammatory cytokines and decreased levels of
anti-inflammatory cytokines. Ample studies have indicated elevated levels of
interleukin (IL)-6, IL-1, tumor necrosis factor-α (TNF α), as well as C-reactive protein (CRP) in aged subjects. among
other cytokines, these cytokines are reported to be high in patients with severe
cases of COVID-19. In which IL-6 plays a key role in contributing to cytokine
storm. Accordingly, it seems that increased generation of
pro-inflammatory markers due to SARS-CoV 2 and aging have a critical role in
the process of cytokine storm in severe COVID-19 patients. Although,
the exact underlying mechanism of cytokine storm in elderly adults with severe COVID-19
infection is far from clear. However, It seems that “cytokine storm” the phenomenon in elderly patients with severe COVID-19 infection is associated
with many age-related pathophysiologic processes, including alteration of
angiotensin-converting enzyme 2 (ACE2) receptor expression, excess ROS
production, alteration of autophagy, senescent adipocytes activity mean the
inflammatory phenotype of senescent cell activity, particularly adipose tissue,
and immune-senescence, as well as lack of vitamin D content. Here, we are going
to review and discuss all above mentioned age-related pathophysiological pathways
that appear to contribute to the dysregulation of cytokine networks and
possibly a cytokine storm in elderly patients with severe COVID-19 infection.
First of these we
will discuss relation between aging and angiotensin‑converting
enzyme 2 receptor (ACE2)
will discuss relation between aging and angiotensin‑converting
enzyme 2 receptor (ACE2)
The renin-angiotensin system (RAS) is an important
regulator of several physiologic events, including cardiovascular
regulator of several physiologic events, including cardiovascular
and blood volume, diabetes, and chronic renal disease.
This system is composed of two different pathways, which have opposing
effects to stimuli which
are angiotensin-converting enzyme (ACE)/angiotensin II (Ang II)/angiotensin
receptor type 1 (AT1) (ACE/Ang II/AT1) pathway; this pathway is related
to tissue injury, inflammation and fibrosis,
This system is composed of two different pathways, which have opposing
effects to stimuli which
are angiotensin-converting enzyme (ACE)/angiotensin II (Ang II)/angiotensin
receptor type 1 (AT1) (ACE/Ang II/AT1) pathway; this pathway is related
to tissue injury, inflammation and fibrosis,
the other pathway
is angiotensin-converting enzyme 2 (ACE2)/Ang 1–7/Mas receptor (ACE2/Ang
1–7/Mas) pathway that exerts anti-inflammatory and anti-fibrosis
effects. Recently, it is well accepted that ACE2 on lung epithelial cells are
the entry-point receptors for COVID-19 particles and making it unattainable to
catalyze the reactions. Unfortunately,
several studies identified that ACE2 expression significantly reduces with
aging. These evidences may partially suggest that the increase concentration of
ACE2 receptors in lung epithelial cells in children and young adults may have a
protective effect on severe clinical manifestations due to COVID-19 infection.
Therefore, it is highly likely that low ACE2 expression with aging can lead to
cytokine storm.
is angiotensin-converting enzyme 2 (ACE2)/Ang 1–7/Mas receptor (ACE2/Ang
1–7/Mas) pathway that exerts anti-inflammatory and anti-fibrosis
effects. Recently, it is well accepted that ACE2 on lung epithelial cells are
the entry-point receptors for COVID-19 particles and making it unattainable to
catalyze the reactions. Unfortunately,
several studies identified that ACE2 expression significantly reduces with
aging. These evidences may partially suggest that the increase concentration of
ACE2 receptors in lung epithelial cells in children and young adults may have a
protective effect on severe clinical manifestations due to COVID-19 infection.
Therefore, it is highly likely that low ACE2 expression with aging can lead to
cytokine storm.
After this
the next topic of our lecture is the relation between
the next topic of our lecture is the relation between
Aging and excess production of ROS
It is well accepted that ROS considered as a signaling Molecule at
low concentrations, and also as a mediator of inflammation at high concentrations.
The main sources of ROS are mitochondrial respiratory chain and NADPH oxidase. It
is suggested that ROS production augment with age and the excess ROS production
in aging can initiate many proinflammatory cytokines generation through activation
of multiple transcription factors, including nuclear factor kappa B (NF-κB), activator protein 1 (AP-1), specificity protein 1 (Sp1), and
peroxisome proliferator-activated receptors (PPARs) and subsequently increased release of pro-inflammatory cytokines,
including; TNF-α, IL-1β, IL-2, and IL-6, as well as adhesion
molecules. Interestingly,
as the excess ROS production can increase pro-inflammatory cytokines, the
pro-inflammatory cytokines can also increase ROS production.
low concentrations, and also as a mediator of inflammation at high concentrations.
The main sources of ROS are mitochondrial respiratory chain and NADPH oxidase. It
is suggested that ROS production augment with age and the excess ROS production
in aging can initiate many proinflammatory cytokines generation through activation
of multiple transcription factors, including nuclear factor kappa B (NF-κB), activator protein 1 (AP-1), specificity protein 1 (Sp1), and
peroxisome proliferator-activated receptors (PPARs) and subsequently increased release of pro-inflammatory cytokines,
including; TNF-α, IL-1β, IL-2, and IL-6, as well as adhesion
molecules. Interestingly,
as the excess ROS production can increase pro-inflammatory cytokines, the
pro-inflammatory cytokines can also increase ROS production.
Hence, excess ROS
production and inflammation are closely related, which are taking part in the
pathogenesis of chronic inflammation and cytokine storm in elderly adults.
production and inflammation are closely related, which are taking part in the
pathogenesis of chronic inflammation and cytokine storm in elderly adults.
Aging and autophagy
Autophagy is a conserved catabolic turnover pathway in eukaryotic
cells by which cellular material delivered into the
cells by which cellular material delivered into the
lysosomes for degradation. Autophagy process is related to the
maintenance of cellular
homeostasis, and its dysregulation could lead to the development of several
aging-related pathophysiological diseases. It has been shown that the autophagy
process, decrease during aging and leads to the accumulation of damaged
macromolecules and organelles. importantly mitochondria, which is the major
source of ROS result in increased ROS production. In this context, two major processes are for
protection from harmful effects of ROS, including mitophagy and antioxidant capacity.
at one side, mitophagy, which is characterized by autophagic degradation of
mitochondria, decreased with aging. On the other hand, decreased mitophagy, together
with decreased antioxidant capacity during aging can increased ROS levels in
the body. The excess production of ROS leads to increase pro-inflammatory
maintenance of cellular
homeostasis, and its dysregulation could lead to the development of several
aging-related pathophysiological diseases. It has been shown that the autophagy
process, decrease during aging and leads to the accumulation of damaged
macromolecules and organelles. importantly mitochondria, which is the major
source of ROS result in increased ROS production. In this context, two major processes are for
protection from harmful effects of ROS, including mitophagy and antioxidant capacity.
at one side, mitophagy, which is characterized by autophagic degradation of
mitochondria, decreased with aging. On the other hand, decreased mitophagy, together
with decreased antioxidant capacity during aging can increased ROS levels in
the body. The excess production of ROS leads to increase pro-inflammatory
cytokine secretion. Although, the exact underlying mechanism of
how the decline in autophagy and a rise in ROS levels during aging can elevate
pro-inflammatory cytokine release is far from clear. However, it is well accepted
that low activity of autophagy process and high level of ROS production during
aging, can activate and upregulate
how the decline in autophagy and a rise in ROS levels during aging can elevate
pro-inflammatory cytokine release is far from clear. However, it is well accepted
that low activity of autophagy process and high level of ROS production during
aging, can activate and upregulate
Nod-like receptors (NLRs). It is observed that activation of
cytosolic NLRs increased during aging. And can increase the production of
pro-inflammatory cytokines, including IL-1β and IL-18. So, it seems that crosstalk
between
cytosolic NLRs increased during aging. And can increase the production of
pro-inflammatory cytokines, including IL-1β and IL-18. So, it seems that crosstalk
between
the decline of mitophagy pathways and elevated ROS level during
aging can imbalance, immune system activity of
aging can imbalance, immune system activity of
elderly adults.
Aging and senescent adipocytes
Senescent cells accumulate with aging in many human tissues,
leading to chronic inflammation and organ dysfunction. Senescent cells have
lower cell viability, as well as insufficient protection against oxidative
stress. Adipose tissue is a dynamic structure that plays an important
contribution in modulating of metabolism and inflammation. It is highly likely
that adipose tissue dysfunction in aged obese subjects leads to more serious
complications of COVID-19 as compared to younger individuals. In obese
COVID-19 patients, the adipose tissue interacts with the immune system and
increased the lethality of the infection by fat tissue-associated cytokines or adipokines
which are released. like amyloid-A which acts directly on macrophages and
increases the generation of pro-inflammatory cytokines. Therefore, the elevated
release of pro-inflammatory cytokines by senescence adipocytes possibly leads
to the elevated risk of the cytokine storm in COVID-19 patients.
leading to chronic inflammation and organ dysfunction. Senescent cells have
lower cell viability, as well as insufficient protection against oxidative
stress. Adipose tissue is a dynamic structure that plays an important
contribution in modulating of metabolism and inflammation. It is highly likely
that adipose tissue dysfunction in aged obese subjects leads to more serious
complications of COVID-19 as compared to younger individuals. In obese
COVID-19 patients, the adipose tissue interacts with the immune system and
increased the lethality of the infection by fat tissue-associated cytokines or adipokines
which are released. like amyloid-A which acts directly on macrophages and
increases the generation of pro-inflammatory cytokines. Therefore, the elevated
release of pro-inflammatory cytokines by senescence adipocytes possibly leads
to the elevated risk of the cytokine storm in COVID-19 patients.
And with this thanks for watching and The remaining part of this
lecture will be covered in the next video. Make sure you have subscribed our
channel so don’t miss it
lecture will be covered in the next video. Make sure you have subscribed our
channel so don’t miss it
